Case 19-2018: A 15-Year-Old Girl with Acute Kidney Injury

To the Editor

We thank Kao et al. (June 21 issue)1 for their discussion but question the diagnosis of atypical hemolytic–uremic syndrome, a disorder we similarly considered in a 3-year-old girl who presented with anemia (hemoglobin level, 78 g per deciliter), thrombocytopenia (platelet count, 22,000 per cubic millimeter), and azotemia (creatinine level, 1.9 mg per deciliter) 3 days after having a single nonbloody, loose stool. We obtained a specimen from a rectal swab and identified Shiga toxin 2 by means of a multiplex gastroenteritis polymerase-chain-reaction assay and subsequently cultured Shiga toxin–producing Escherichia coli (STEC) O121.2 After 13 hospital days and three erythrocyte transfusions, the patient was discharged with improving renal function. The course described by Kao et al. closely resembles typical hemolytic–uremic syndrome, especially considering the antecedent bloody diarrhea. The nonspecific markers of complement dysfunction are unconvincing, and persistently undetectable activity in the alternative complement pathway, according to the AH50 assay, is attributable to eculizumab.3 As Kao et al. state, the detection of STEC depends on the nature of the assay performed.4,5 Consequently, we believe that it is likely that the case patient had hemolytic–uremic syndrome caused by a non-O157 STEC. In all such cases, we encourage rapid specimen acquisition6 and serotype-independent testing for STEC by means of nucleic acid amplification tests, culture, or both.

Silviu Grisaru, M.D.
Byron Berenger, M.D.
Stephen Freedman, M.D.C.M.
University of Calgary, Calgary, AB, Canada

Dr. Freedman reports that bioMérieux, which manufactures the FilmArray gastrointestinal panel, has provided his research with group devices and test kits. No other potential conflict of interest relevant to this letter was reported.

  1. 1. Case Records of the Massachusetts General Hospital (Case 19-2018). N Engl J Med 2018;378:24212429.

  2. 2. Chui L, Couturier MR, Chiu T, et al. Comparison of Shiga toxin-producing Escherichia coli detection methods using clinical stool samples. J Mol Diagn 2010;12:469475.

  3. 3. Willrich MAV, Andreguetto BD, Sridharan M, et al. The impact of eculizumab on routine complement assays. J Immunol Methods 2018;460:6371.

  4. 4. Qin X, Klein EJ, Galanakis E, et al. Real-time PCR assay for detection and differentiation of Shiga toxin-producing Escherichia coli from clinical samples. J Clin Microbiol 2015;53:21482153.

  5. 5. Parsons BD, Zelyas N, Berenger BM, Chui L. Detection, characterization, and typing of Shiga toxin-producing Escherichia coli. Front Microbiol 2016;7:478478.

  6. 6. Freedman SB, Xie J, Nettel-Aguirre A, et al. Enteropathogen detection in children with diarrhoea, or vomiting, or both, comparing rectal flocked swabs with stool specimens: an outpatient cohort study. Lancet Gastroenterol Hepatol 2017;2:662669.


The discussant replies: Atypical hemolytic–uremic syndrome is a clinical diagnosis with multisystem involvement. Decreased complement function occurs in only 30 to 50% of patients.1 The patient described in the case had a frame-shift mutation in CFHR3, not previously described, which we believe is likely to be causal. Six months into treatment, when the dosing interval for eculizumab was changed from 2 weeks to 3 weeks, her serum creatinine level increased. A previous report described two patients with end-stage renal disease whose treatment was initially based on a diagnosis of STEC hemolytic–uremic syndrome but who were found to have complement abnormalities as a part of pretransplantion workup.2 It is speculated that complement plays a role in STEC hemolytic–uremic syndrome.3,4 The case we described highlights the point that the diagnosis of atypical hemolytic–uremic syndrome should be considered in patients whose symptoms are severe. Complement abnormalities may be the host factor that leads to the phenotype associated with such severe symptoms.

Amita Sharma, M.D.
Massachusetts General Hospital, Boston, MA

Since publication of her article, the author reports no further potential conflict of interest.

  1. 1. Kavanagh D, Goodship TH, Richards A. Atypical haemolytic uraemic syndrome. Br Med Bull 2006;77-78:522.

  2. 2. Alberti M, Valoti E, Piras R, et al. Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations. Am J Transplant 2013;13:22012206.

  3. 3. Noris M, Mescia F, Remuzzi G. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol 2012;8:622633.

  4. 4. Morigi M, Galbusera M, Gastoldi S, et al. Alternative pathway activation of complement by Shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis. J Immunol 2011;187:172180.

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